Allylation reagent and process for allylating a nucleophile

ABSTRACT

A process and reagent for allylating a nucleophile preferably of formula (V). 
     
         (R).sub.n Ar--Y--H                                         (V) 
    
     The nucleophile is reacted with a reagent containing an allyl derivative and a catalyst in an aqueous phase containing at least one element of group VIII of the Classification of the elements. A water-soluble phosphine may also be present in the reagent, and the reagent may also contain at least one organic phase.

The present invention relates to a process for the synthesis of allylcompounds. It relates more particularly to the allylation of anilinessuch as meta-trifluoromethylanilines.

N-Allylations of amides, and in particular of anilides, anilines andphenol, are often difficult and necessitate the use of reagents such asalkyl halides, which are expensive and generate large amounts of salinewastes.

The N-allylation of anilides is an important step in the synthesis ofmany compounds. The reaction can lead either to mono- orpolyallylations, which can be of paramount importance when it is desiredto obtain one type of allylation which is more selective with respect tothe others. For example, during the synthesis ofN-allyl-N-dichloroacetyl-meta-trifluoromethylanilide, an intermediate inthe synthesis of an important herbicide, the step of allylation ofmeta-trifluoromethylaniline (m-TFMA) has to be a mono-allylation whichis as selective as possible with respect to the diallylation.

One of the objects of the present invention is to provide a processwhich is capable of allylating anilides even when they are deactivatedby electron-attracting groups.

Another object of the present invention is to provide a process which iscapable of allylating anilines using inexpensive and readily accessiblereagents.

Another object of the present invention is to provide a process which iscapable of allylating anilines even when the anilines are deactivated byelectron-attracting groups.

Another object of the present invention is to provide a process which iscapable of allylating phenols even when the latter are deactivated byelectron-attracting groups.

Another object of the present invention is to provide a process which iscapable of allylating any nucleophilic substrate, in particular anonionic nucleophilic substrate (such as organometallic compounds), evenone as poor as amides.

Another object of the present invention is to provide an allylationreagent which is usable for the above process.

These and other objects which will become apparent hereinafter areachieved by means of a process employing an allylating reagentcontaining at least:

an allyl derivative, preferably allyl ether, a source of allyl ether, orallyl alcohol, and

a catalyst containing at least one element of group VIII of the PeriodicClassification of the elements (Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt)(see. Bull. Soc. Chim. 1966 No. 1 supplement).

The allyl derivative is preferably of formula (III):

    Z--O--C(R.sub.1)(R.sub.2)--C(R.sub.3)═C(R.sub.4)(R.sub.5)(III)

wherein:

R₁ represents a hydrogen or an alkyl radical, preferably containing 1 or2 carbon atoms;

R₂ represents a hydrogen or an alkyl radical, preferably containing 1 or2 carbon atoms;

R₃ represents a hydrogen or an alkyl radical;

R₄ represents a hydrogen or an alkyl radical;

R₅ represents a hydrogen or an alkyl radical;

wherein the term "alkyl" includes the term "aryl" and Z represents ahydrogen atom or a residue derived from an alcohol (including phenols)by removal of a hydroxyl group,

a catalyst containing at least one element of group VIII of the PeriodicClassification of the elements.

The ether may be made "in situ" from alcohol(s). It is preferable thatthe stationary content of ether is such that the ether/alcohol ratio isgreater than 1/2%, more preferably greater than 5% and most preferablybetween 10% and 20%.

The term alkyl is employed with the meaning given in the DuvalDictionary of Chemistry, with the additional feature that it can alsoinclude an aryl group.

It is preferable that at least 2, more preferably 3 and most preferably4 of the radicals R₁ to R₅ have at most two carbon atoms; however, atleast one of the radicals R₁ to R₅ may be such that the allyl alcohol isa heavy alcohol, for example of the aromatic series, of the terpine typeor of the steroid series.

Thus, at least 1 radical and at most 3 radicals R₁ to R may bepolycyclic aryl radicals, fused or otherwise, homo- or heterocyclic.Said reagent can, in the process according to the present invention, bebrought into contact with any nucleophilic substrate, in particular anon-anionic nucleophilic substrate. The anionic species are, forexample, those which are supposedly active in organometallic compounds,especially in the case of synthesis via carbanions. The species renderednucleophilic by stripping out mobile hydrogen to form a carbanion aresupposedly anionic, including phenols and anilines deactivated by atleast one electron-attracting substituent on, or by the presence of ahetero atom in, the aromatic ring-system.

The reaction also gives very good results when the aromatic ring-systemis deactivated by the presence of attracting group(s).

A deactivated aryl radical is one depleted of electrons, and with anelectron density at most equal to that of benzene, or at most similar tothat of a halobenzene. This depletion may be due to the presence of ahetero atom in the aromatic ring when it has six members, such as inpyridine or quinoline.

Naturally, the electron depletion may also be caused byelectron-attracting groups; the low electron content may be due to bothof these causes.

Thus, the deactivated aryl preferably carries at least one substituentselected from groups which attract by a donor effect or by a mesomericeffect as defined in the reference work in organic chemistry "AdvancedOrganic Chemistry" by M. J. MARCH, 3rd edition, published by WILEY,1985; see, in particular pp. 17 and 238. Examples of attracting groupsare NO₂, CF₃, CN, COX (X=Cl, Br, F, OR), CHO, Cl, Br.

The allylation gives particularly good results when the process isapplied to a compound of formula (V):

    (R).sub.n Ar--Y--H                                         (V)

wherein:

Ar represents a monocyclic aromatic radical which may be homocyclic orheterocyclic or Ar represents a polycyclic aromatic radical which may befused or non-fused and may also be homo- or heterocyclic,

R represents at least one substituent selected independently fromhydrogen, chlorine, bromine, saturated or unsaturated and optionallysubstituted linear, branched or cyclic alkyl (including aryl) radicals,ether, and optionally substituted radicals selected from alkoxy,aryloxy, amino, hydroxyl, carboxylate, acyloxy, ester, amido, nitrileand acid radicals,

n is an integer greater than or equal to 1, preferably equal to 1, 2, 3or 4,

Y represents a chalcogen atom, preferably an oxygen atom, or a group NR'with R' representing a light acyl having 1 to 10, preferably 1 to 6 andmore preferably 2 to 5 carbon atoms, and optionally polyhalogenated,preferably mono-, di- or trihalogenated, a light alkyl (including aryl)having 1 to 10, and preferably 1 to 6, carbon atoms, or a hydrogen atom.

Particularly useful are the deactivated anilines of formula II:

    A--Ar--N--H.sub.2                                          (II)

wherein:

A represents a substituent as defined by R, preferably an attractinggroup, in particular perfluoroalkyl, or a hydrogen atom;

Ar has the same meaning as above and the phenols having formula IV:

    (R).sub.n Ar--O--H                                         (IV)

wherein:

Ar, R and n have the same meaning as above.

Thus, the reaction can also give very good results when the aromaticring is deactivated by the presence of attracting group(s). The totalnumber of carbon atoms in the substrates rarely exceeds 50, althoughthere is no contra-indication for heavier substrates.

The following are preferable reaction conditions for carrying out thereaction. The temperature is preferably above room temperature and belowor equal to the refluxing temperature. When it is appropriate to work atother temperatures, a temperature of between 100° C. and 300° C. may beused, preferably between 100° C. and 200° C., although the temperaturesare given by way of example and should not be considered as limiting.

The pressure used is preferably the equilibrium pressure of the reagentat the temperature of use. A higher pressure may also be used.

The reaction is preferably conducted in the absence of an oxidizingagent, particularly oxygen, which has the drawback of oxidizingphosphines or equivalent compounds. The reactions are preferablyconducted under an inert atmosphere (such as a rare gas, nitrogen,etc.), on previously outgassed reactants if the phosphines or equivalentcompounds used are especially susceptible to degradation.

The allylation can be, in particular, an N, O or C allylation. When theallyl radical is palindromic, the direction of allylation is of littleimportance. Otherwise, as a guide, the allylation takes placeessentially according to the rules known to those skilled in the art, atthe 1- or 3-position of the allyl radical, in which rules the hindranceplays an important part (allylation via the less hindered side).

When the ether is a phenol ether, the preponderant allylation is aninternal C-allylation at the ortho position. Thus, when the allylationis carried out on a phenol (an alcohol in the broad sense), the phenolether obtained may rearrange by an internal C-allylation at the orthoposition, liberating the phenol function for a second allylation.

The metals giving the best catalytic results are the platinum oremetals; however, it may be economically advantageous to use lightermetals on account of their much lower cost. In the platinum ore metalfamily, each metal has specificities which makes it more or lessadvantageous according to the case.

As an example, in the allylation of anilides, the metal generally givingthe best result is palladium, usually activated by at least onepnictine. However, when the anilide is derived from an alpha-halogenatedacid or, generally speaking, when the substrate has an activatedhalogen, palladium catalysis can lead to many byproducts. In thesecases, it has been demonstrated that the use of platinum, preferablyactivated by at least one pnictine (arsine, stibine, phosphine, etc.)gives results which are both significant and selective.

In the case of the allylation of bi- or polysubstitutable compounds, itis desirable not to increase the kinetics of the reaction excessively,particularly when carrying out only a mono- or oligoallylation. In thesesituations, agents may be added which retard the reaction, such asantimony trioxide or bismuth trioxide.

When the selectivity between oligo- and polyallylation is notsufficient, it is possible to improve selectivity by varying the excessof allyl ether, or its derivative, relative to the substrate, forexample by limiting the stoichiometric excess with respect to thedesired reaction to 1/2, preferably to 1/4 and more preferably to 1/10,or alternatively by working with an excess of substrate.

Thus, the present invention constitutes an improvement over the priorart by providing a spectrum of reagents which can have varied subtledifferences which can be used and adapted to many different cases.

The catalytic features of the elements of group VIII may be modified bycoordinating agents. Such agents may be selected from organicderivatives of the elements of group V which are known to havecoordination capacity, such as phosphines, arsines, stibines ornitrites, in particular aromatic nitrites such as benzonitrile, andoxygen-containing organic compounds of these elements of group V, forexample, phosphorous acid esters, phosphonates and phosphinates.Preferred elements of group V are those whose period is of a higher rankthan that of the period of nitrogen.

The coordinating agents are advantageously hydrocarbon derivatives ofthe elements of group V. The hydrocarbon derivatives of the elements ofgroup V are derived from nitrogen such as amines, from phosphorus suchas phosphines, from arsenic such as arsines and from antimony such asstibenes. These compounds are, by analogy with the term pnictide,designated in the present description by the term pnictines. They arepreferably selected from the hydrocarbon derivatives of phosphorus suchas phosphines.

The catalyst may contain, as a pnictine, a trialkylphosphine, preferablya triphenylphosphine. The phosphine and the metal of group VIII arepreferably in the form of tetrakis(phosphine)-metal.

Some weakly nucleophilic substrates are slow to react; thus in order toaccelerate the allylation, a small amount of stannous salt, such asSnCl₂, may be added. At most the salt is added in a quantity equal tothe amounts of the metal of group VIII, but preferably approximatelytenfold less in molar terms of the stannous salts.

It should be emphasized that one of the important objects of the presentinvention is to provide a reagent which permits the desired allylation,especially a monoallylation. The presence of stannous salts stronglypromotes the diallylation of anilines.

For this reason, it is preferable that the catalyst has as low a tincontent as possible. The mole ratio of tin to the element of group VIIIof the Periodic Classification of the elements is preferably less than10⁻², and more preferably less than 10⁻⁴.

In the case, to which the invention is more especially directed, whereit is desired to carry out an N-monoallylation on an aniline deactivatedby at least one electron-attracting substituent, alkylation, includingallylation, is a special case which virtually failed to proceed. Thismakes the results obtained by carrying out the present invention all themore surprising.

However, the compounds of group V A (N, P, As, Sb, Bi) may also bepresent in the form of trivalent oxides, such as arsenious oxide, whichare not excluded from the above compounds and can give better results,not functioning to the detriment of monoallylation.

In general, these compounds significantly increase the kinetics of thereaction. In this case, the element of group V B is generally arsenic.

The catalyst may contain, as compounds of the elements of group V, atrialkylphosphine, preferably a triphenylphosphine. The phosphine andthe metal of group VIII are preferably in the form oftetrakis(phosphine)-metal.

In the context of the present invention, a metal catalyst may be used inelemental form (oxidation number zero) or in oxidized form. Thesecatalysts can take the form of salts, oxides or complexes. The catalystscan be used in aqueous phase. Examples of the salts, oxides andcomplexes of the metals mentioned above, in the oxidation state II, arepalladium chlorides, palladium acetate and palladium chloride complexedwith benzonitrile. The co-anions are of little importance, whereas thecations are of significance.

An example of a complex of the metals in the oxidation state zero is(dibenzylideneacetone)palladium.

It is preferable to use an amount of catalyst such that the mole ratioof the metal catalyst to the compounds of the elements of group V, whichare in the form of coordinating agents, often designated by the termligand, is between 2:1 and 100:1, and preferably from 4:1 to 30:1. Themole ratio of the oxides of group V to the metal catalyst is generallybetween 1:100 and 100:1 preferably from 5:100 to 10:1 and mostpreferably approximately 1:1.

The reaction can take place in, and the reagent contain, any solvent,including those capable of acting as a solvent A or B as describedlater, such as:

benzene and aromatic solvents,

alkanes having at least 6 carbon atoms,

water,

acetonitrile,

benzonitrile,

dimethylformamide,

N-methylpyrrolidone,

nitrobenzene.

However, when the reaction is performed in an aprotic solvent, inparticular a nonaqueous solvent, and/or when the allyl derivativecontains an ether group, it is preferable to use weakly basic solventshaving a donor number less than that of tetrahydrofuran (20), preferablyat most equal to that of diethyl ether, more preferably 10 and mostpreferably 5. The inhibitory character of the solvents may be used toincrease the selectivity of the oligo- and monoallylation; preferablythe solvent is used in a molar amount less than that of the substrate.

It is, in this case, desirable to avoid solvents including the last 4 onthe list given as an example (or, more precisely, as a paradigm in theclassical and grammatical sense of the term). The absence of a solventor the use of the substrate or of a component of the reagent may then bea good approach. It should be recalled that the donor number, sometimesdesignated by the acronym DN, is defined by the value of the change inenthalpy delta-H due to the association of the solvent with antimonypentachloride in dilute methylene chloride medium.

The amount of solvent used is such that the concentration of the metalof group VIII is greater than 10⁻⁵ M, and preferably from 10⁻² to 10⁻³ Min the solvent. This preference applies to the aqueous phase in theevent of use of the latter alone or in a two-phase system.

Preferred are the reactions without a solvent or in which the substrateis the solvent, those in which the solvent is the allylating agent, inparticular the allyl derivative, and those in which the solvent is anaqueous phase.

The reaction may also use water-soluble pnictines as pnictines, and usean aqueous reagent.

To render the coordinating agents, and in particular the pnictines,water-soluble, polar groups imparting water-solubility may be grafted,taking care not to create in this manner nucleophiles which would beliable to interfere with the reaction.

It is possible to graft neutral groups such as polyols but, in view ofthe strong lipophilicity of pnictines, it is preferable that the graftedgroups are ionic, cationic such as quaternary ammonium groups, oranionic such as any group constituting the associated base of acids,preferably strong acids. In the latter case, carboxyl, sulfonic orphosphonic groups are examples.

French Patent No. 2,366,237 or French Patent No. 2,549,840, which arehereby incorporated by reference, relate to groups used for modifyingphosphines.

Water-soluble phosphines include the solubletriphenylphosphinetrisulfonates P(C₅ H₄ --SO₃ --)₃, for example ofalkali metals, and those of formula P(C₅ H₄ --CO₂ H)₃, preferably inanionic form.

A preferred embodiment of the present invention uses a two-phase systemin which one of the two liquid phases is an aqueous phase in which themetal of group VIII is solubilized in the aqueous phase by awater-soluble phosphine or equivalent compound. This technique greatlyfacilitates recovery and recycling of the catalyst, which recycling isone of the key parameters of the profitability of this type of processon account of the ever-increasing cost of platinum ore metals. Moreover,the yields are not significantly impaired by the use of two liquidphases.

Unexpectedly, the use of an aqueous phase can enable the monoallylationto be accelerated considerably without a concomitant acceleration ofpoly- and, in particular, diallylation. It is thus much easier toperform a selective oligoallylation relative to a polyallylation. Whenthe selectivity provided by the use of the aqueous phase is notsufficient, it is possible to vary the excess of allyl derivative, forexample of allyl ether or its derivative, relative to the substrates.The excess alkyl derivative may be varied by limiting the stoichiometricexcess with respect to the desired reaction to 1/2, preferably to 1/4and more preferably to 1/10, or alternatively by working with an excessof substrate.

In another preferred embodiment of the present invention, it is possibleto use a two- or multiphase system in which one of the liquid phases isan aqueous phase. In particular, when the substrate, the allylderivative such as the allyl ether and/or the end product are onlyslightly soluble in the aqueous phase, it is possible to perform thereaction, either without the addition of a solvent in a multiphasesystem, or by adding an intermediary solvent B, or by adding a solventA, or by adding an intermediary solvent B and solvent A.

The solvents A are organic solvents selected in such a way that theydissolve at least 1%, and preferably at least 2%, by mass of thesubstrate, and are sufficiently hydrophobic not to be miscible withwater in all proportions.

It is preferable that water can dissolve at most only 10% of solvent A,and preferably at most 1%, by mass, even in the presence of thesubstrate as an intermediary solvent.

It is preferable that solvent A can dissolve at most only 10% of water,and preferably at most 1%, by mass, even in the presence of thesubstrate as an intermediary solvent.

The solvents A can be mixtures, including petroleum cuts. Under theworking conditions, the solvents A must be inert with respect to thesubstrates and reactants used.

The preferred families of solvents A are selected from the groupconsisting of hydrocarbons, aromatic derivatives, ethers, esters andhalogenated solvents. Preferably, these solvents should be lessnucleophilic than the substrates, so as not to interfere with thereaction, unless the substrate is in excess in order to play a solventrole.

Examples of these families are halogenated derivatives such asdichloromethane, 1,2-dichloroethane and 1,1,1-trichloroethane, aromaticderivatives such as toluene and halogenated aromatic derivatives such aschlorobenzene, esters such as ethyl acetate and isopropyl acetate, andethers such as tert-butyl methyl ether, anisole, and heavy alcohols,which satisfy the constraints of immiscibility as specified above.

For reasons of industrial economy, it is preferable that solvent A isdistilled at atmospheric pressure or under coarse or higher vacuum.

If the substrates are not water-soluble, an intermediary solvent B maybe added to solvent A, which solvents can be mixtures whose role will beto solubilize the substrate and/or, where appropriate, the allylderivative or the specific allyl ether in the aqueous phase, and whichwill distribute between the aqueous and organic phases when the latterexists initially.

It is preferable that the water can dissolve at least 1/10 ofintermediary solvent B, and preferably at least 1/3, by mass, even inthe presence of the catalyst with its coordinating agents.

The intermediary solvent is preferably added in a sufficient amount forthe amount of substrate and/or, where appropriate, the allyl ether orother allyl derivative, soluble in the aqueous phase, to be at least ofthe same order of magnitude (within a factor of ten) as the amount ofcatalyst present in the aqueous phase at the beginning of the reaction.

Subject to the above preferences, solvents which are usable asintermediary solvents, are water-soluble solvents of the alcohol,nitrile, ether (especially cyclic), acid, sulfone, sulfoxide, amide,alkyl phosphate, alkyl phosphonate, alkyl phosphinate, phosphine oxideand ketone types, or even of the type comprising an amine which is notnucleophilic, in particular, through a steric effect.

It is also possible to select solvent A such that it also plays the partof an intermediary solvent B. In this case, solvents are used whichpossess a polar function of the type possessed by the intermediarysolvents, and which have a lipophilic chain selected in such a way thatwater dissolves said intermediary solvent in the proportion ofapproximately 1/100 to 1/10 by mass.

Solvent A and/or solvent B, depending on the case, can be the allylether or derivative.

The present invention also contemplates the replacement of said allylderivative by one of the derivatives of allyl alcohol capable of givingan ether or an alcohol in situ under the conditions of the allylationreaction. Further the present invention contemplates use as a source ofthe allyl radical of a mixture of allyl ether and/or alcohol with otherprecursors of the allyl radical.

Another objective of the present invention is an allylation reagentemploying a reagent which is as inexpensive as allyl ethers, and inparticular employing the above reagent.

This objective is achieved by means of the allylation reagent, whichcontains:

an allyl alcohol or allyl ether derivative of the formula (III):

    Z--O--C(R.sub.1)(R.sub.2)--C(R.sub.3)═C(R.sub.4)(R.sub.5)(III)

wherein:

R₁ represents a hydrogen or an alkyl radical, preferably containing 1 or2 carbon atoms;

R₂ represents a hydrogen or an alkyl radical, preferably containing 1 or2 carbon atoms;

R₃ represents a hydrogen or an alkyl radical;

R₄ represents a hydrogen or an alkyl radical;

R₅ represents a hydrogen or an alkyl radical, and Z represents ahydrogen atom or a residue derived from an alcohol by removal of ahydroxyl group,

a catalyst containing at least one element of group VIII of the PeriodicClassification of the elements.

The allylation reagent may or may not contain a solvent, and may or maynot contain an aqueous phase.

Another reagent according to the present invention contains:

an aqueous phase;

an allyl alcohol or one of its derivatives;

a catalyst containing at least one element of group VIII of the PeriodicClassification of the elements, said element of group VIII of thePeriodic Classification being maintained in the aqueous phase bycomplexing with at least one water-soluble coordinating agent (orligand).

This reagent may or may not contain a solvent. A solvent A may bepresent which is not completely miscible with the aqueous liquid phase.A solvent B may be present providing, in the aqueous phase, for aminimal solubility of the lipophilic substrates.

Said allyl alcohol or one of its derivatives is preferably selected fromthe derivatives of formula (III'):

    Z'--O--C(R.sub.1)(R.sub.2)--C(R.sub.3)═C(R.sub.4)(R.sub.5)(III')

wherein:

R₁, R₂, R₃, R₄, and R₅ have the same definition as above and where Z'represents an acyl radical, preferably having at most 10 carbon atoms,or preferably hydrogen.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a kinetic graph of product yield with respect to the initialsubstrate. The FIGURE shows that the substrate, m-TFMA decreases in %quickly with a correlated strong increase of the monoallylated compound,whereas the formation of the diallylated compound is delayed andincreases slowly compared to the monoallylated compound. The graphdemonstrates the ease of obtaining selective monoallylation.

The whole invention will be described more completely by means of theexamples which follow, which must in no case be considered to belimiting.

In the examples which follow, the following definitions apply: ##EQU1##

GENERAL PROCEDURE

The reactants, solvents and catalysts were introduced in the statedproportions into the container in which the reaction took place.

This operation was carried out in a glove box placed under nitrogen, theingredients being outgassed beforehand in order to remove oxygen. Whenthe boiling point of the reaction mixture was above the testtemperature, either a reactor or a sealed tube or a Schott tube wasused. Where not otherwise specified, a sealed tube was used.

When the temperature was above the boiling point, one of the two tubeswas used. Where not otherwise specified, a sealed tube was used.

The other reaction conditions are specified in the examples whichfollow. Except where otherwise stated, the reactants used were asfollows:

allyl alcohol;

palladium;

triphenylphosphine. The allyl ether used was (H₂ C═CHCH₂)₂ O unlessphenol was present at which point the allyl ether was an ether of allyland phenol.

EXAMPLE 1

Reactants

m-TFMA: 2 mmol (m-TFMA=meta-trifluoromethylaniline)

Pd(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

1 equivalent allyl ether: 2 mmol

Results

    ______________________________________            DC allyl DC          CY     CY    As.sub.2 O.sub.3            ether    (m-TFMA)    (N-Allyl)                                        (Diallyl)    ______________________________________    0%      49        46         87     16    5%      91       100         20     79    ______________________________________

EXAMPLE 2

m-TFMA: 2 mmol

Pd(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

1/2 equivalent allyl ether: 1 mmol

Results

    ______________________________________            DC allyl DC          CY     CY    As.sub.2 O.sub.3            ether    (m-TFMA)    (N-Allyl)                                        (Diallyl)    ______________________________________      0%    89       68          80     12    4.5%    99       79          78     21    ______________________________________

EXAMPLE 3 Study of Pd(Pφ₃)₄ and Pt(Pφ₃)₄

Reactants

m-TFMA: 2 mmol

Allyl ether: 1 mmol

Catalyst: 2 mol %

4 h at 90° C. with stirring

Result

    ______________________________________            DC allyl DC          CY     CY    Catalyst            ether    (m-TFMA)    (N-Allyl)                                        (Diallyl)    ______________________________________    Pt(Pφ.sub.3).sub.4            32       14          74     12    4.1%    Pd(Pφ.sub.3).sub.4            89       68          80     12    4.5%    ______________________________________

Comment

Pd(Pφ₃)₄ was markedly more reactive than Pt(Pφ₃)₄ for the sameselectivity.

EXAMPLE 4 Influence of B₂ O₃

Reaction

m-TFMA+allyl ether→N-allyl-TFMA+diallyl-TFMA

Reactants

m-TFMA: 2 mmol

Pd(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

Allyl ether: 6.5 mmol

Result

    ______________________________________            DC allyl DC          CY     CY    B.sub.2 O.sub.3            ether    (m-TFMA)    (N-Allyl)                                        (Diallyl)    ______________________________________    5%      69       100         2      99    ______________________________________

EXAMPLE 5 Comparative Reactivity of Allyl Ether and Alcohol

Reaction

m-TFMA+1-propanol→N-allyl-TFMA+N,N-diallyl-TFMA

1-Propenol=allyl alcohol

Reactants

m-TFMA: 2 mmol

Pd(Pφ₃)₄ : 2%

As₂ O₃ : 1.1%

1 h at 90° C.

Result

    ______________________________________    Allylating             DC            CY       CY    agent    (m-TFMA)      (N-Allyl)                                    (Diallyl)    ______________________________________    Allyl alc.             78            65       31    11.5 mmol    Allyl eth.             99            19       82    11.5 mmol    ______________________________________

Furthermore, the allyl alcohol and ether were assayed:

    ______________________________________    DC (allyl alcohol) =                  74       CY (allyl ether) =                                        31    DC (allyl ether) =                  35       CY (allyl alcohol) =                                         2    ______________________________________

EXAMPLE 6 Comparative Reactivity of Allyl Ether and Alcohol

Reactants

m-TFMA: 2.1 mmol

Pd(Pφ₃)₄ : 2.2%

15 min at 90° C.

Result

    ______________________________________    Allylating             DC            CY       CY    agent    (m-TFMA)      (N-Allyl)                                    (Diallyl)    ______________________________________    Allyl alc.             8             61       26    2.1 mmol    Allyl eth.             7             50       20    1 mmol    ______________________________________

Furthermore, the allyl alcohol and ether were assayed:

    ______________________________________    DC (allyl alcohol) =                  19       CY (allyl ether) =                                        3    DC (allyl ether) =                   5       CY (allyl alcohol) =                                        5    ______________________________________

EXAMPLE 7 m-TFMA Allylation with Allyl Ether+Pt^(II) +TPPTS

In a 30-cc Schott tube:

H₂ O: 5.109 g

PtCl₂ (COD): MW=374; 56.1 mg; 0.15 mmol

COD=1,5-cyclooctadiene

TPPTS (0.522 mmol/g): 1.6458 g (0.859 mmol) in water.

(TPPTS=sodium triphenylphosphinetrisulfonate)

m-TFMA: 1.1442 g; MW=161.1; 7.1024 mmol

allyl ether: MW=98.15; 1.5613 g; 15.907 mmol ##EQU2## Reaction time=1 h30 min at 90° C.; the mixture was then cooled to room temperature andextracted with ethyl acetate, and the phases were separated aftersettling had taken place.

The analysis was carried out by gas chromatography on the organic phase,and gave the following results:

DC=18.5%

N-Allyl: CY>95%

Diallyl: CY<0.2%

EXAMPLE 8 Influence of As₂ O₃

Reactants

Phenol: 2 mmol

Pd(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

1 equivalent of allyl ether: 2 mmol

Result

    ______________________________________             DC allyl DC         CY     CY    As.sub.2 O.sub.3             ether    (Phenol)   (O-Allyl)                                        (C-Allyl)    ______________________________________    0%       61       39         18     41    5%       70       59         23     26    ______________________________________

EXAMPLE 9 Influence of the Catalyst

Reactants

Phenol: 2 mmol

Pd(Pφ₃)₄ or Pt(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

1/2 equivalent: 1 mmol

Result

    ______________________________________    Catalyst                DC     CY     CY    2%     As.sub.2 O.sub.3                    DC      (Phenol)                                   (O-Allyl)                                          (C-Allyl)    ______________________________________    Pt(Pφ.sub.3).sub.4           4.2%     29      12     60      13    Pd(Pφ.sub.3).sub.4           4.5%     68      38     30      28    ______________________________________

EXAMPLE 10 Single Organic Phase

Reactants

m-TFMA: 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

1 h at 90° C. with stirring

Result

    ______________________________________    m-TFMA     DC         CY Mono  CY Di    ______________________________________               31         60       13    ______________________________________

EXAMPLE 11 Two-Phase (Organic/Aqueous)

Reactants

H₂ O: 5 ml

Allyl alcohol: 3.3 ml (66 mmol)

m-TFMA: 2 ml (16 mmol)

TPPTS: aqueous solution 0.522 mmol/g; T=90° C.

Result

    ______________________________________              TPPTS    Catalyst  Metal    Time    DC    TY (%)    (mmol)    Mole ratio                       (h)     (%)   N-Allyl                                           N-Diallyl    ______________________________________    Pd(OAc).sub.2              5.2      0.75    81    80     1    (0.16)    PtCl.sub.2 (COD)              6.5      5.5     94    76    18    (0.12)    RhCl(COD)/2              4.5      3.5     74    n.d.  n.d.    (0.19)    RuCl.sub.3              5.4      3.5     96    78    17    (0.16)    NiCl.sub.2 /NaBH.sub.4              4.6      2.5      8     8    --    (0.2)    ______________________________________     n.d = reaction product identified but yield not measured

Comment

Pd: The first allylation was very rapid. Sampling of the organic phaseenabled it to be assessed (see FIG. 1).

Pt: Same reaction profile as above but with lower activity.

Ni: The reduction of NiCl₂ with sodium borohydride in the presence ofTPPTS lead to the formation of Ni(TPPTS)₄, of a characteristic redcolor.

EXAMPLE 12 Organic/Aqueous Two-Phase System

Reactants

Anilide (meta-trifluoromethylacetanilide): 1.08 g (5.32 mmol)

Allyl alcohol/anilide: 5.92

Allyl alcohol: 1.83 g (31.5 mmol)

Pd^(II) Ac₂ : 70 mg; MW=224.49; 0.31 mmol; Pd^(II) /anilide=5.86%

TPPTS (0.522 mmol/g): 2.39 g (1.2476 mmol)

H₂ O: 2.35 g

TPPTS/Pd^(II) : 4.05

16 h 30 min at 139° C.-140° C.

Anilide: DC<10%

Allyl anilide: TY=7%

EXAMPLE 13 Comparative Organic/Aqueous Two-Phase System: Role of theAllyl Unsaturation Test with 1-propanol

Reactants

Aniline (meta-trifluoromethylaniline): 1.2 g (7 mmol)

PtCl₂ : 53 mg; MW=374; 0.14 mmol;

TPPTS (0.522 mmol/g): 1.6 g (0.84 mmol)

H₂ O: 5.1 g

1-Propanol: 2.2 g (37 mmol)

Reaction time: 1 h 48 min at 90° C.

The reaction mixture was taken up with ethyl acetate and the latterphase was subjected to an assay by gas chromatography:

Aniline: DC<3%

Propylated aniline: TY=0%

From this result, the need for the presence of the allyl unsaturationwas deduced.

EXAMPLE 14 Catalysis by the System Tetrakis(Triphenylphosphine)-Pd(Pφ₃)₄/Arsenious Anhydride

Amide: 4 mmol

Allyl alcohol: 1.5 ml (22 mmol)

Pd(Pφ₃)₄ : 2% (0.08 mmol)

As₂ O₃ : 4% (0.16 mmol)

Manipulations carried out under inert atmosphere

Ar=m--CF₃

    ______________________________________                                     DC                                     (amide)    Amide     Catalyst    Conditions (%)   CY (%)    ______________________________________    ArNHCOCH.sub.3              Pd(Pφ.sub.3).sub.4 /As.sub.2 O.sub.3                           90° C. - 17 h                                     22    100    ArNHCOCH.sub.3              Pd(Pφ.sub.3).sub.4                          140° C. - 17 h                                     88    90    ArNHCOCH.sub.3              Pd(Pφ.sub.3).sub.4 /As.sub.2 O.sub.3                          140° C. - 17 h                                     70    89    ArNHCOCHCl.sub.2              Pd(Pφ.sub.3).sub.4                          140° C. - 17 h                                     86.5  trace    ______________________________________

a) Reaction performed in a 30-ml reactor

b) Reaction performed in a sealed tube.

EXAMPLE 15 Use of Pt(Pφ₃)₄

Reaction

N-Dichloroacetyl-m-TFMA+allyl alcohol→NAND+H₂ O cat.

where

NAND=N-allyl-N-dichloroacetyl-meta-trifluoromethylaniline

m-TFMA=meta-trifluoromethylaniline.

Reactants

N-Dichloroacetyl-m-TFMA: 2 mmol

Allyl alcohol: 13 mmol

Pt(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

Results

    ______________________________________                   DC       CY    As.sub.2 O.sub.3                   (Dichloro)                            (NAND)    ______________________________________      0%           11       80-100    8.7%           14       68    ______________________________________

Comments

The reaction took place with a relatively low reactivity but a goodselectivity. As₂ O₃ has only a slight influence.

EXAMPLE 16

Reactants

Acetanilide: 2 mmol

Allyl alcohol: 12 mmol

Pd(Pφ₃)₄ : 2.3 mol %

4 h at 90° C. with stirring

Results

    ______________________________________                             CY    Reactant           DC    (estimated)    ______________________________________    p-Methoxyacetanilide                       66    10    Acetanilide        31    75    ______________________________________

EXAMPLE 17 Role of Stannous Chloride

Reactants

m-TFMA: 2 mmol

PtCl₂ : 2 mol % (0.08 mmol)

4 h at 90° C. with stirring

Excess of allyl alcohol, which also plays the part of a solvent, or 1equivalent dissolved in diglyme. SnCl₂ was added in variable amounts.

Results

    ______________________________________    Mole ratio       DC (%)      CY     CY    Sn/Pt %  Solvent (m-TFMA)    (N-Allyl)                                        (Diallyl)    ______________________________________    0        all. alc.                     92.5        79      6    1        all. alc.                     96.5        72     18    2        all. alc.                     100         29.5   68.5    0        diglyme 22          66      1    2        diglyme 70          77      7.5    3        diglyme 76          73.5   13.5    ______________________________________

In all cases, the presence of tin chloride was detrimental to themonoallylation although the yields are substantially improved. Theunfavorable effect of diglyme on the reaction and the relativelyfavorable effect on the selectivity were noted.

EXAMPLE 18 Platinum With Another Oxidation Number and Without a Pnictine

The reactions were carried out at 70° C. for 3 h.

m-TFMA=4 mmol

Catalyst=2% (0.08 mmol)

    ______________________________________    Catalyst DC (m-TFMA)  CY N-Allyl                                    CY Diallyl    2% (mol) (%)          (%)       (%)    ______________________________________    H.sub.2 PtCl.sub.6             57.5         38        0    ______________________________________

This example shows that coordinating agents of the halide type,especially of the first 3 periods, suffice, in particular, for platinum.

EXAMPLE 19 Catalysis by Pd(Pφ₃)₄

    ______________________________________           Catalyst DC (m-TFMA) CY N-Allyl                                        CY Diallyl    Test   (2 mol %)                    (%)         (%)     (%)    ______________________________________    169-32 Pd(Pφ.sub.3).sub.4                    22          83      9    ______________________________________

Test performed at 70° C. for 3 h using 4 mmol of m-TFMA, 4 mmol of allylalcohol and 1.2 ml of diglyme.

In order to preserve the qualities of the catalyst, the reactor wascharged under an inert atmosphere in a glove box.

Under the same working conditions, PtCl₂ gave a DC=22%, CY N-allyl=66%and CY diallyl=1%.

The activity of Pd(Pφ₃)4 may hence be compared with that of platinum(II), with a slight gain in N-allyl compound.

EXAMPLE 20 Influence of Arsenious Anhydride

    ______________________________________          Catalyst   DC (m-TFMA)                                CY N-Allyl                                        CY Diallyl    Test  (mol%)     (%)        (%)     (%)    ______________________________________    150-18          As.sub.2 O.sub.3                   2%     9        0      0    (a)    161-28          Pd(Pφ.sub.3).sub.4                   2%    100      5.5     95.5    (a)   As.sub.2 O.sub.3                   4%    169-31          Pd(Pφ.sub.3).sub.4                   2%    75.5     55      40.5    (b)   As.sub.2 O.sub.3                   4%    169-32          Pd(Pφ.sub.3).sub.4                   2%    22       83      5    (b)    151-20          PtCl.sub.2                   2%    13.5     45      0    (b)   As.sub.2 O.sub.3                   4%    143-7 PtC1.sub.2                   2%    22       66      1    ______________________________________     (a): mTFMA = 4 mmol, allyl alcohol = 22 mmol, 70° C., 3 h     (b): mTFMA = 4 mmol, allyl alcohol = 4 mmol, diglyme

1.2 ml, 70° C., 3 hours

It was established that the gain in reactivity provided by addingarsenious anhydride to the reaction medium is observed with Pd(Pφ₃)₄.

EXAMPLE 21 Role of the Elements of Group V

Reactants

m-TFMA: 2 mmol

Allyl alcohol: 11.2 mmol; Pt- or Pd(Pφ₃)₄ : 2 mol %

Cocatalyst: 4 mol %

4 h at 90° C. with magnetic stirring

Results

    ______________________________________    Catalyst  DC           CY Mono  CY Di    ______________________________________    Pd        35           70        8    Pt        68           67       28    Pd/As.sub.2 O.sub.3              99           14       89    Pt/As.sub.2 O.sub.3              100           1       99    Pd/Sb.sub.2 O.sub.3              22           74        9    Pt/Sb.sub.2 O.sub.3              55           64       13    ______________________________________

EXAMPLE 22 Influence of Cocatalysts

Reactants

m-TFMA: 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

Cocatalyst: 4 mol %

4 h at 90° C. with magnetic stirring

Results

    ______________________________________    Cocata.  DC          CY Mono  CY Di    ______________________________________    Bi.sub.2 O.sub.3             22          82        7    B.sub.2 O.sub.3             74          70       31    ______________________________________

EXAMPLE 23 Role of the Substrate

Reactants

Aniline: 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

4 h at 90° C. with stirring

Results

    ______________________________________                         CY Mono   CY Di    Reactant    DC       (estimated)                                   (Estimated)    ______________________________________    p-Methoxyaniline                97       12        88    Aniline     97       0.2       66    p-Nitroaniline                13       95         0    n-TFMA      35       70         8    ______________________________________

EXAMPLE 24

Reactants

Aniline: 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

As₂ O₃ : 4 mol %

4 h at 90° C. with stirring

Results

    ______________________________________                         CY Mono   CY Di    Reactant    DC       (estimated)                                   (Estimated)    ______________________________________    p-Methoxyaniline                100       1        100    Aniline     99       0.6       90    p-Nitroaniline                40       100        0    m-TFMA      99        14       89    ______________________________________

EXAMPLE 25 Kinetics

Reactants

m-TFMA (meta-trifluoromethylaniline): 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

As₂ O₃ : 5 mol %

Results

    ______________________________________    m-TFMA     DC          CY Mono  CY Di    ______________________________________    4 h - 90° C.                99         14        89    3 h - 90° C.*               100          6       100    2 h - 90° C.               100         19        93    1 h - 90° C.               100          2       100    ______________________________________     *(4% AS.sub.2 O.sub.3)

EXAMPLE 26 Temperature Reduction

Reactants

TFMA (meta-trifluoromethylaniline): 2 mmol

Allyl alcohol: 11.2 mmol

Pd(Pφ₃)₄ : 2 mol %

As₂ O₃ : 4 mol %

Results

    ______________________________________    m-TFMA     DC          CY Mono  CY Di    ______________________________________    1 h - 90° C.*               100          2       100    1 h - 80° C.               100         11       87    1 h - 70° C.                99         12       89    1 h - 60° C.                99         10       90    ______________________________________     *(As.sub.2 O.sub.3 5.4%)

We claim:
 1. An allylating reagent containing:an aqueous phase and at least one organic phase, an allyl derivative, and a water-soluble catalyst in said aqueous phase containing at least one element of group VIII of the Periodic Classification of the elements, wherein said catalyst also contains a coordinating agent which is a water-soluble phosphine.
 2. The reagent as claimed in claim 1, wherein said allyl derivative corresponds to formula (III):

    Z--O--C(R.sub.1)(R.sub.2)--C(R.sub.3)═C(R.sub.4)(R.sub.5)(III)

wherein: R₁ represents a hydrogen or an alkyl radical, R₂ represents a hydrogen or an alkyl radical, R₃ represents a hydrogen or an alkyl radical; R₄ represents a hydrogen or an alkyl radical; R₅ represents a hydrogen or an alkyl radical; and Z represents a hydrogen atom or a residue derived from an alcohol by removal of a hydroxyl group; the total number of carbon atoms in the allyl derivative being at most equal to
 50. 3. The reagent as claimed in claim 2, wherein at least one of R₁ and R₂ contains 1 or 2 carbon atoms.
 4. The reagent as claimed in claim 1, wherein and said element of group VIII is platinum.
 5. The reagent as claimed in claim 1, wherein the element of group VIII is a platinum ore metal.
 6. The reagent as claimed in claim 1, wherein said element is palladium.
 7. The reagent as claimed in claim 1 wherein said coordinating agent is pnictine.
 8. The reagent as claimed in claim 7, wherein said pnictine is trialkylphosphine.
 9. The reagent as claimed in claim 1, wherein said water-soluble phosphine is sodium triphenylphosphinetrisulfonate.
 10. The reagent as claimed in claim 1, comprising two immiscible liquid phases, one of which is said aqueous phase which contains said water-soluble phosphine.
 11. The reagent as claimed in claim 1, wherein said coordinating agent and said metal of group VIII are in the form of tetrakis(phosphine)-metal.
 12. The reagent as claimed in claim 1, wherein said catalyst further contains an oxide of an element of group V A of the Periodic Classification of the elements.
 13. The reagent as claimed in claim 12, wherein said oxide is in the trivalent state.
 14. The reagent as claimed in claim 12, wherein said oxide is arsenic.
 15. The reagent as claimed in claim 1, wherein said allyl derivative contains an ether group or a mixture wherein at least one allyl derivative contains an ether group.
 16. The reagent as claimed in claim 1, wherein said allyl derivative contains an alcohol group or a mixture wherein at least one allyl derivative contains an alcohol group.
 17. The reagent as claimed in claim 1, wherein said allyl derivative is allyl alcohol.
 18. The reagent as claimed in claim 1, wherein said allyl derivative is symmetrical.
 19. The reagent as claimed in claim 1, wherein the total number of carbon atoms in the allyl derivative is
 30. 20. An allylating reagent containing:an aqueous phase, an allyl derivative, a water-soluble pnictine in said aqueous phase, and a water-soluble catalyst containing at least one element of group VIII of the Periodic Classification of the elements.
 21. The reagent as claimed in claim 20, wherein said water-soluble pnictine is a water-soluble phosphine. 